Role of ceRNA network in inflammatory cells of rheumatoid arthritis / 中南大学学报(医学版)

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.

Effect of GSK-3β-mediated DRP1 on inhibition of primary hippocampal neuronal growth induced by aluminum / 环境与职业医学

Background Aluminum (Al) can cause irreversible damage to neurons and synapses function, and the mechanism may be connected to mitochondrial damage caused by glycogen synthase kinase-3β (GSK-3β) regulating dynamin-related protein 1 (DRP1), resulting in inhibition of the growth of neuronal protrusions. Objective To investigate the role of GSK-3β regulating DRP1 in the inhibition of primary hippocampal neurite growth induced by Al. Methods Neurons were extracted from the hippocampus of newborn mice (≤24 h old) for primary culture. On day 6, the purity of neurons was detected by immunofluorescence. On day 10, neurons with good growth state were selected for Al exposure and GSK-3β inhibitor SB216763 (SB) intervention. The experiment design included a blank control group, a dimethyl sulfoxide (DMSO) group, an Al (20 μmol·L−1) group, a SB (1 μmol·L−1) group, and a SB (1 μmol·L−1) + Al (20 μmol·L−1) group. After primary hippocampal neurons were treated with Al or SB for 48 h, cell viability was detected by CCK-8 assay, the mitochondrial morphology of primary hippocampal neurons was observed by transmission electron microscopy, the total protrusion length of primary hippocampal neurons was scanned and analyzed by laser confocal imaging, and their complexity was analyzed by Sholl analysis. The expression levels of phospho-GSK-3β, GSK-3β, and DRP1 were detected by Western blotting. Results The immunofluorescent results showed that the purity of primary neurons was higher than 90%. After the Al exposure and the SB intervention for 48 h, compared with the blank control group, there was no obvious difference in cell viability in the DMSO group and the SB group (P>0.05), and the Al group showed reduced cell viability (P=0.006); there was no obvious difference in cell viability between the SB+Al group and the Al group (P>0.05). Compared with the blank control group, there was no obvious difference in the average total length of protrusion in the DMSO group and the SB group (P>0.05), and the Al group showed reduced average total length of neurite (P<0.001); the average total neurite length in the SB+Al group was significantly increased compared with that in the Al group (P=0.001). The results of Sholl analysis revealed that, within 130 μm from the cytosol, the number of intersections of neurons in each group increased with the increase of distance. Above 130 μm from the cytosol, the number of intersections of neurons in each group decreased gradually with increase of distance. At 130 μm and 310 μm from the cytosol, compared with the blank control group, the number of neuronal intersections in the DMSO group and the SB group had no obvious difference (P>0.05), and that in the Al group was significantly reduced (P<0.05); there was no obvious difference in the number of neuronal intersections between the SB+Al group and the Al group (P>0.05). The mitochondrial structure of the blank control group was complete and the crest was clearly visible; there was no apparent variation in the mitochondrial structure in the DMSO group and the SB group; the mitochondria in the Al group were vacuolated and the crista disappeared; the SB+Al group showed clearer crista than the Al group. The difference in GSK-3β phosphorylation level among groups was statistically significant (F=45.841, P<0.001). Compared with the blank control group, the GSK-3β phosphorylation level showed not significantly different in the DMSO group (P>0.05), increased in the SB group (P=0.022), and significantly reduced in the Al group (P<0.001); the GSK-3β phosphorylation level was significantly higher in the SB+Al group than in the Al group (P<0.001). The difference in DRP1 protein level among groups was statistically significant (F=8.389, P=0.003). Compared with the blank control group, the DRP1 protein levels in the DMSO group and the SB group were not significantly different (P>0.05), and significantly increased in the Al group (P=0.001); the DRP1 protein level in the SB+Al group was significantly lower than that in the Al group (P=0.029). Conclusion Al may increase the level of DRP1 protein by activating GSK-3β, causing mitochondrial damage and inhibiting neuronal protrusions growth.

Establishment of normal foot and common foot disease models using three-dimensional finite element method and biomechanical analysis / 中国组织工程研究

BACKGROUND: In the field of trauma orthopedics, three-dimensional finite element analysis is only a routine means of biomechanical evaluation and internal fixator design and optimization in the treatment of internal fixation of fractures, but also provides new directions for the basic and clinical researches of trauma orthopedics. OBJECTIVE: To establish a three-dimensional finite element model of normal foot, flatfoot, equinus, and foot fracture and to undergo biomechanical analysis. METHODS: One healthy volunteer and patients with flatfoot, equinus, and foot fracture were selected. Their feet were scanned by CT. Three-dimensional finite element modeling and biomechanical analysis were performed by using computer three-dimensional imaging technology according to the CT data. The stress distribution and stress values of each model were then obtained for comparative analysis. The study was approved by the Ethics Committee of Mindong Hospital Affiliated to Fujian Medical University. RESULTS AND CONCLUSION: The three-dimensional finite element models of normal foot, flatfoot, equinus, and foot fracture were established and biomechanical analysis was performed. In the patients with flatfoot, the stress values of the metatarsus and tarsus were significantly increased compared with the normal values. The stress of the equinus was mainly concentrated around the ankle joint, especially on the talus surface. The simple metatarsus fracture had little effect on the stress changes in the tarsus area. The stress in the tarsus area of the Lisfranc injured patients was increased more obviously than in the normal feet. In this study, the three-dimensional finite element modeling and biomechanical analysis of the foot combines computer technology with clinical practice, which provides reference for biomechanical research of human foot. The numericalization of the mechanical data of different foot conditions by mechanical analysis provides important mechanical basis for the clinical treatment of the foot.

Thyroid lymphoma progressed with Hashimoto's thyroiditis diagnosed by core-needle biopsy : case report and literature review / 中华内分泌代谢杂志

Objective To explore the significance of core-needle biopsy ( CNB) in the diagnosis of thyroid lymphoma. Methods A case of Hashimoto's thyroiditis for several decades, showed a thickening of the neck for several months, and no abnormalities were found by the method of fine-needle aspiration( FNA), then we performed CNB and flow cytology. Results Thyroid lymphoma was finally diagnosed through CNB and flow cytology. Conclusion Thyroid lymphoma should be considered when the neck became thickened in short time in patients with chronic Hashimoto's thyroiditis. Core-needle biopsy accompanied with flow cytometry and immunohistochemistry analysis should be suggested as routine diagnostic method especilly when fine-needle aspiration was negative.

Clinical image identification of basal cell carcinoma and pigmented nevi based on convolutional neural network / 中南大学学报(医学版)

To construct an intelligent assistant diagnosis model based on the clinical images of basal cell carcinoma (BCC) and pigmented nevi in Chinese by using the advanced convolutional neural network (CNN).
 Methods: Based on the Xiangya Medical Big Data Platform, we constructed a large-scale clinical image dataset of skin diseases according to Chinese ethnicity and the Xiangya Skin Disease Dataset. We evaluated the performance of 5 mainstream CNN models (ResNet50, InceptionV3, InceptionResNetV2, DenseNet121, and Xception) on a subset of BCC and pigmented nevi of this dataset. We also analyzed the basis of the diagnosis results in the form of heatmaps. We compared the optimal CNN classification model with 30 professional dermatologists.
 Results: The Xiangya Skin Disease Dataset contains 150 223 clinical images with lesion annotations, covering 543 skin diseases, and each image in the dataset contains support for pathological gold standards and the patient's overall medical history. On the test set of 349 BCC and 497 pigmented nevi, the optimal CNN model was Xception, and its classification accuracy can reach 93.5%, of which the area under curve (AUC) values were 0.974 and 0.969, respectively. The results of the heatmap showed that the CNN model can indeed learn the characteristics associated with disease identification. The ability of the Xception model to identify clinical images of BCC and Nevi was basically comparable to that of professional dermatologists.
 Conclusion: This study is the first assistant diagnosis study for skin tumor based on Chinese ethnic clinical dataset. It proves that CNN model has the ability to distinguish between Chinese ethnicity's BCC and Nevi, and lays a solid foundation for the following application of artificial intelligence in the diagnosis and treatment for skin tumors.

Maternal zinc metabolism and changes of metallothionein-1 and zinc transporter-1 in fetal congenital heart diseases / 中华临床营养杂志

Objective To investigate maternal zinc metabolism and the changes of zinc-related factors as metallothionein-1 (MT1) and zinc transporter-1 (ZnT1) in certain types of congenital heart diseases (CHD).Methods Fifteen infants with interventricular septal defect,12 infants with atrial septal defect and 7 infants with tetralogy of Fallot,together with their mothers were enrolled,and normal infants and their mothers were enrolled by a ratio of 1 ∶ 1 with the above three types of CHD diseases.General conditions of the mothers,along with their diets and zinc-containing drug supplementation during the pregnancy,were surveyed.Maternal blood zinc levels and serum alkaline phosphatase activities at gestation week 32 and delivery or induced abortion,and the protein and mRNA expressions of MT1 and ZnT1 in maternal serum and placental tissue at delivery or induced abortion were assayed.Results The general conditions were comparable between the CHD group and control group.The ratio of the mothers taking more zinc-rich food was significantly lower in the CHD group than in the control group.Circulating zinc levels in interventricular septal defect (73.55±5.79 μmol/L),atrial septal defect (72.66±5.82 μmol/L) and tetralogy of Fallot (68.72±6.72 μmol/L) groups were significantly lower than those in the control groups (82.77± 7.88,84.58 ± 7.55 and 85.66 ± 7.30 μmol/L) at delivery (P all ＜ 0.05).Similar change patterns were seen for serum alkaline phosphatase activities.The relative quantities of serum MT1 and ZnT1 proteins in interventricular septal defect (73.22±36.54 and 68.55± 27.82),atrial septal defect (64.29± 38.26 and 74.55 ± 29.67) and tetralogy of Fallot (67.88± 30.50 and 70.13±29.65) groups were significantly lower than those in their corresponding control groups (166.31±67.43and 97.67±30.22,182.56±71.40 and 111.65±32.70,and 173.81±62.36 and 108.27±28.52,P＜0.01 or P＜0.05).The relative quantities of placental MT1 and ZnT1 proteins and mRNA expressions in interventricular septal defect (protein quantities 0.438±0.096 and 0.384±0.061,mRNA expressions 1.23±0.82 and 0.96±0.39),atrial septal defect (0.427±0.093 and 0.377±0.059,1.17±0.70 and 0.85±0.40) and tetralogy of Fallot (0.414±0.111 and 0.336±0.066,1.31±0.97 and 0.90±0.38) groups were significantly lower than those in their corresponding control groups (protein quantities 0.565±0.083 and 0.541±0.090,mRNA expressions 2.78± 1.06 and 1.67±0.33;protein quantities 0.622±0.136 and 0.493±0.079,mRNA expressions 2.85±0.89 and 1.72±0.38;protein quantities 0.637±0.125 and 0.521±0.089,mRNA expressions 3.21 ± 0.99 and 1.61±0.29;P＜0.01 or P＜0.05).Conclusion Mothers with their fetus of certain types of CHD are found zinc deficiency,and down-regulation of MT1 and ZnT1 expressions in the serum and placenta may involve in the pathogenesis of CHD when maternal zinc deficiency.

Interaction network of differentially expressed genes between Kashin-Beck disease and osteoarthritis / 中华地方病学杂志

Objective To investigate the data of gene expression microarray by protein interaction network analysis,establish an interaction network of differentially expressed genes between Kashin-Beck disease (KBD) and osteoarthritis (OA) and choose the central nodes of the network.Methods The articular cartilage samples of degrees Ⅱ ° and Ⅲ ° KBD and OA patients were selected according to the national diagnosis criteria for KBD and the Western Ontario and McMaster Universities (WOMAC) for OA.Chondrocytes of 8 patients with KBD and 7 with OA were selected.About 1 000 different genes detected by gene expression microarray were inputted into STRING 9.1 database online for analysis and establishment of the interaction network.The interaction data were imported into Cytoscape 3.2.1 software for screening the central nodes of the network.KEGG database was exploited for pathway analysis and functional study of the central node genes,Real-time PCR (RT-PCR) was used for verification.Results The protein products of 334 differentially expressed genes between KBD and OA had interrelation,forming a complicated interaction network.About 150 central nodes were selected by Cytoscape 3.2.1 that involved in more than ten signal pathways involved in mitochondria,bone metabolism and inflammatory cytokine.Conclusion The interaction network of the differentially expressed genes between KBD and OA,especially the central nodes of this network,can provide clues to the mechanism and early diagnosis and molecular targeted therapy of KBD and OA.

Effects of Exercise on Expressions of Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B in Injured Spinal Cord of Rats / 天津医药

Objective To investigate the effects of exercise on expressions of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) in spinal cord of spinal cord injury (SCI) rats. Methods Spinal cord injury models were produced by universal spinal cord impact system. Twenty-four Sprague-Dawley rats were randomly divided into 3 groups, exercise group (SCI-induction and exercises, n=8), control group (SCI-induction without exercises,n=8) and sham-operation group (no operation, without SCI nor exercises, n=8). Exercise training began from the 7th day after injury for 4 weeks. The locomotor function was assessed by Basso-Beattic-Bresnahan (BBB) scale before injury and at the 1st, 2nd, 3rd, 4th and 5th week post injury. The expressions level of BDNF and TrkB in spinal cords were detected by immunohistochemis-try and Western blot. Results Since the 3rd week after injury (after 2 weeks of exercise training), BBB scores in exercise group were higher than that in control group (P ＜ 0.05). In immunohistochemistry test, positive immunologic reaction to BDNF protein was mainly located in anterior horn of spinal cord, and the expression level in exercise group was significantly higher than that in sham-operation group and control group (P＜0.05). In immunohistochemistry test, positive immunologic reaction to TrkB protein was located in anterior horn and dorsal horn and central canal of spinal cord, and the expression lev-el in exercise group was significantly higher than that in sham-operation group and control group (P＜0.05). Expression of BDNF and TrkB in exercise group rats after exercise for 4 weeks were significantly increased, compared with that in control group. Conclusion Exercise training may effectively induce BDNF and TrkB expression in spinal cords and promote the re-covery of locomotor function of SCI rats.

Survey on smoking status and risk factors in residents / 中华全科医师杂志

A survey on smoking status and risk factors was conducted among 3373 residents in two districts of Shen yang city during November 2008 and September 2009 ; the pulmonary function tests were also performed for all subjects.A logistical regression model was used to evaluate the risk factors of smoking,and the knowledge about diseases caused by smoking was evaluated by chi-square test.The overall smoking rate was 50.7％ ( 1710/3373 ) ; 86.8％ (1458/1680) for males a(un)14.9％ (252/1693)for females.The risk factors of smoking ( P ＜ 0.05 ) in order of OR value were as follows:drinking,work environment and underlying diseases ; the protective factors were:female,educational level,overweight ( BMI ≥ 24) and old age.The survey on knowledge of smoking-related disease was conducted in 2478 residents including 815 smokers and 1663 non-smokers. The awareness levels about whether smoking can cause COPD,asthma,birth defects,malignant tumor,abortion,growth retardation,fetal death and myocardial infarction were significantly different between smokers and non-smokers.

Determination of Cyromazine and Dicyclanil Residues on Greasy Wool by High Performance Liquid Chromatography / 分析化学

A method for the determination of cyromazine and dicyclanil residues on greasy wool was developed with HPLC and confirmed with HPLC-MS/MS.The cyromazine and dicyclanil residues on greasy wool were extracted with 1% trichloroacetic acid solution with ultrasonic, and cleaned up by MCX SPE column.The HPLC separation was performed on a Hypersil NH_2 using water-acetonitrile (V/V) as the mobile phase with gradient elution and detected at the wavelength of 214 nm.The corroboration method of HPLC-MS/MS was used with electro-spray ionization of positive ion mode.The [ M + H ]~+ and characteristic ions of dicyclanil were m/z 191.0, 150.0 and 163.0, and cyromazine were m/z 167.0, 85.0 and 125.0.The linear ranges of cyromazine and dicyclanil were 0.05-5.0 mg/L.There were good linear relationships between the peak area and concentration in the linear range.The correlation coefficient was 0.9999.The detection limit of cyroma zine was 0.02 mg/kg, and dicyclanil was 0.01 mg/kg.The average recoveries of cyromazine and the dicycla nil were 95.0%-99.9% and 83.6%-92.2%, respectively.

Expression of the transcription factor GATA-4 in human heart development / 医学研究生学报

Objective: To investigate the expression of the transcription factor GATA-4 in human heart development.Methods: Immunohistochemistry was used to detect the expression of GATA-4 in 45 normal human embryonic hearts of 6-23 gestational weeks.Results: In the early stage of the fetal heart morphogenesis,we observed no GATA-4 expression in the ventricle,weak expression in the atria and relatively high expression in the trabecular nets.With the heart development,the GATA-4 expression was enhanced in the atria,ventricle,trabecular nets and atrial-ventricular valves,as well as in the muscular and membranous interventricular septum,the highest in each part of the heart.Conclusion: The transcription factor GATA-4 plays an important role in human heart development.

The value of hysteroscopy in the diagnosis and treatment of infertility caused by intrauterine adhesions / 中国微创外科杂志

Objective To study the value of hysteroscopy in the diagnosis and treatment of infertility women caused by intrauterine adhesions. Methods 32 cases of infertility caused by intrauterine adhesions received hysteroscopic diagnosis, classification and treatment. The postoperative pregnancy rate was observed. Results The hysteroscopic diagnosis and score of infertility caused by intrauterine adhesions included 19 cases of gradeⅠ, 11 cases of gradeⅡ, 2 cases of grade Ⅲ. After hysteroscopic surgery and the related treatment, the postoperative menorrhea improved rate was 65.7%(21/32), and pregnancy rate was 62.5%(20/32). Conclusions Hysteroscopy is accurate , safe ,effective and may be used as the first choice in the diagnosis and treatment of infertility caused by intrauterine adhesions.

Epidemiologic analysis of greenhouse farmer's lung in part of rural areas of Liaoning province / 中国实用内科杂志

Objective To survey the prevalence of greenhouse farmer's lung and related risk factors in part of rural areas of Liaoning Province.Methods Using uniform scheme,procedures and questionnaire,a survey for 5420 farmers(2660 men and 2760 women)with complete data who work inside greenhouses was performed in Shenyang,Xinmin,Chaoyang,and Jinzhou between August 2006 and June 2009.Pulmonary function tests was performed for every active farmer.Results Greenhouse farmer's lung was diagnosed in 308 cases,205 men(66.55%,205/308)and 103 women(33.44%,103/308),a prevalence of 5.7%(308/5420).The prevalence rate of greenhouse farmer's lung in males was significantly higher than that in females(?2=39.93,P0.05).In the 308 cases,the number of patiernts presented with fever chill,cough/sputum,chest tightness/shortness of breath were 180(58.44%),192(62.34%),160(51.95%)respectively,and the number of crepitations,radiological changes,spirometry abnormalities and serum IgE antibodies(+)was 164(53.25%),153(49.68%),147(47.73%)and 136(44.16%)at the time of the study.62.34%(192/308)of patients with greenhouse farmer's lung were mild and 38.66%(116/308)were severe.Conclusion The total prevalence rate of greenhouse farmer's lung in part of rural areas of Liaoning Province was 5.7% and multiple risk factors were associated with the disease.

Application of hysteroscopy in the diagnosis and treatment of infertility caused by intrauterine factors / 中国微创外科杂志

Objective To study the value of hysteroscopy in the diagnosis and treatment of infertility caused by intrauterine lesions. Methods Hysteroscopic examinations and operations were performed in 82 cases of infertility caused by intrauterine lesions. Results No abnormal findings were found in 4 cases,while the other 78 cases of intrauterine abnormity comprised 23 cases of endometrial polyp, 29 cases of adhesive uteritis,18 cases of submucous myoma or adenomyosis, and 6 cases of uterine deformity. After hysteroscopic surgery and related treatment, the postoperative pregnancy rate reached 62 32% (43 of 69). Conclusions Hysteroscopy may be effectively used in the diagnosis and treatment of infertility caused by intrauterine factors.